Term
| METHOTREXATE mechanism of action against dividing neoplastic cells |
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Definition
-can't make folate, so can't make cells rapidly
-has high affinity for DHFR (dihydrofolate reductase)
-inhibits production of N5N10MeFH4, cofactor required for reaction that produces dTMP -> so you can't make DNA precursors, so basically you can't make any new cells |
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Term
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Definition
-damages the oral and gastric mucosa
-bone marrow
-nephro toxicity
-teratogenic
(rapidly dividing cell populations) |
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Term
Methotrexate
mechanisms of resistance |
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Definition
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Term
| Treatment of Stage I, II or III (non-metastatic or low-risk metastatic) gestational trophoblastic neoplasia (GTN or out of control mole) |
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Definition
Low dose methotrexate as single agent (without leucovorin)
-stage II or III maybe hysterectomy if future fertility is not a concern |
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Term
| Treatment of stage II/III high risk metastatic gestational trophoblastic neoplasia (GTN or out of control mole) |
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Definition
| High dose methotrexate as single agent with leucovorin rescue |
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Term
| Treatment of stage IV high risk metastatic gestational trophoblastic neoplasia (GTN or out of control mole) |
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Definition
-Surgery
-Radiation
-High dose methotrexate as single agent with leucovorin rescue |
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Term
| What is the mechanism of Leucovorin rescue when administered 24 hours after Methotrexate? |
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Definition
Replenishes N5N10MeFH4 cofactor so that cells can make dTMP
(normal cells are better at transporting Leucovorin than tumor cells, so this "rescues" normal cells while tumor cells are still being killed by Methotrexate) |
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Term
| Treatments for Retinoblastoma (Small Tumors) |
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Definition
1. Surgery (Enucleation-Eye removal)
2. Radiation Therapy: plaque
3. Cryotherapy
4. Photocoagulation |
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Term
| Treatments for Retinoblastoma (Any size tumor) |
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Definition
6. Chemo/size reduction (so that one of the treatments for small tumors can be used, ie surgery)
7. Opthalmic arterial infusion (concentrated chemo)
8. Subtenon chemo
9. High dose chemo with stem cell transplant (severe cases) |
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Term
| What is the Log-Kill Hypothesis basically saying? |
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Definition
| The sooner tumors are detected (the fewer tumor cells are present), the less likely the patient will die. |
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Term
| What's the definition of the Log Kill Hypothesis? |
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Definition
| A given dose of a chemo drug kills a constant proportion of a cell population rather than a constant number of cells. The log-kill hypothesis proposes that the magnitude of tumor cell kill by anticancer drugs is a logarithmic function. |
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Term
| Log Kill Hypothesis Graph |
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Definition
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Term
| Why is it effective to use chemo drugs in combination? |
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Definition
1. Prevents resistance
2. Combination of cell cycle specific and cell cycle nonspecific allows growing and at rest cells to be targeted
3. Additive and Synergystic MOA
4. Different toxicities, less myelosupression |
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Term
| Cell Cycle Specific or Cell Cycle Non-Specific |
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Definition
CCS: Inhibit DNA synthesis during the S phase
CCNS: Alkylate and damage DNA, push cells into apoptosis; work on replicating or non-replicating cells, so works for slow growth tumors |
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Term
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Definition
Class: Alykylating agent
-drug is activated then nucleophilic attack of unstable aziderine ring by electron donor
-pushes metabolism to toxic metabolite which kills tumor cells |
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Term
| Cyclophosphamide Toxicity |
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Definition
Acrolein toxic metabolite accumulates in the bladder
-give MESNA to get rid of it
Can increase chance of leukemia |
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Term
| Cyclophosphamide MOR (mechanisms of resistance) |
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Definition
*Require active p53 to use, so not in Li Fraumeni
-SH group can mutate
-enhanced DNA repair can make alkylating ineffective |
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Term
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Definition
Class: Intercalating agent, arthocycline antibiotic
Three MOAs:
1. Intercalates with DNA and inhibits replication and transcription
2. Forms oxygen free radicals --> forms semiquinone and damages DNA=apoptosis
3. Inhibits Topoisomerase II -> double straded breaks (inhibits reparing DNA after breaking it) |
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Term
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Definition
Cardiac Toxicity, give iron chelator
Myelosuppression |
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Term
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Definition
Exfflux via pump
Decreased transport
Decreased Topoisomerase |
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Term
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Definition
Inhibits Topoisomerase I and thus produces DNA damage
-given as a prodrug, must be cleaved to active form in the liver (SN38) |
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Term
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Definition
Terrible diarrhea
Myelosuppression |
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Term
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Definition
| Decreased accumulation of drug in tumor cells |
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Term
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Definition
Alkaloid (derived from bacteria)
-Intercalates with DNA, binds with Fe
-Produces reactive oxygen species
-Stops cell cycle in G1 |
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Term
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Definition
Pulmonary fibrosis (bc lungs lack hydrolase)
-pt. that have been on bleomycin have to have more oxygen when under anesthesiology
-has very low myelosuppression, yay! |
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Term
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Definition
| hydrolase enzyme cleaves it to inactive form |
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Term
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Definition
alkylator
-produces crosslinks in DNA --> DNA damage --> apoptosis
*req. active p53 |
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Term
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Definition
NEPHROTOXICITY
Hearing loss
Severe nausea and vomiting
Moderate myelosuppression |
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Term
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Definition
Cleared fairly quickly
Loss of mismatch repair proteins=resistance
*req. active p53 so can't use with Li Fraumeni patients |
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Term
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Definition
Forms reactive platinum complexes that form intrastrand and crosslinks in DNA -->DNA damage
-invented to be less cytotoxic than Cisplatin |
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Term
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Definition
| Peripheral neuropathy (tingly fingers and toes) |
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Term
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Definition
Decreased levels in tumor cells
Less resistance than Cisplatin |
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Term
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Definition
Prodrug, activated by addition of a ribose and then a phosphate group = active form: FdUMP
-directly inhibits Thymidylate Synthase, so tumor cells can't make dTMP, so they can't make DNA and replicate, etc
-also inhibit RNA processing; incorporate themselves into DNA
-almost always give with leucovorin in order to increase TS production |
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Term
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Definition
Nausea
Mucosa lining degredation
Alopecia
-quickly replicating cell populations die |
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Term
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Definition
| Decreased enzymes, ie Thymidylate Synthase |
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Term
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Definition
Must be metabolized to active form by HPRTase
-Inhibits several enzymes of de novo purine nucleotide synthesis
-Incorporated into RNA/DNA, leads to damage thus apoptosis |
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Term
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Definition
Bone marrow suppression
May lead to leukemia |
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Term
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Definition
Decreased drug transport into cell
Increased drug efflux out of cell |
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Term
| Vinblastine and Vincristine MOA |
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Definition
| Blocks mitosis by inhibiting tubulin synthesis--> halts cell division=cell death |
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Term
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Definition
Huge myelosuppression ("blasts" the bone marrow)
Neuro toxicity
Less GI than Vincristine |
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Term
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Definition
Less myelosuppression
Neuro tox (central and peripheral neuropathy --> tingly, hearing loss, muscle weakness)
GI tox |
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Term
| Two Factors that Contribute to Multidrug Resistance |
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Definition
1. P-Glycoprotein pump
-acquired resistance
-drugs pumped out
2.Mutations/loss of p53
-loss of apoptosis
-defects in the mismatch repair enzyme family |
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Term
| Name three drugs that require an active p53 in order to work |
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Definition
cyclophosphamide
cisplatin
oxaloplatin
-in Li Fraumeni, you have to be careful with giving chemo because you may mess up normal cells (deactivate p53) and promote another tumor |
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Term
| Treatment for Basal Cell Carcinoma |
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Definition
-surgery
-topical chemo,5-FU
-laser therapy |
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Term
| Treatment for Squamous Cell Carcinoma |
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Definition
-surgery
-topical chemo,5-FU
-laser therapy
-regional lymph removal or irradiation
-cisplatin used for stage III |
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Term
| Melanoma Treatment, based on stage |
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Definition
Stage I: Surgery
Stage II: Surgery + immunotherapy
Stage III: Surgery + lymph dissection + maybe chemo
Stage IV: No treatment available, usually, BRAF drug is new (not on test) |
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